▪ Abstract Breathing is a vital behavior that is particularly amenable to experimental investigation. We review recent progress on three problems of broad interest. (i) Where and how is respiratory rhythm generated? The preBotzinger Complex is a critical site, whereas pacemaker neurons may not be essential. The possibility that coupled oscillators are involved is considered. (ii) What are the mechanisms that underlie the plasticity necessary for adaptive changes in breathing? Serotonin-dependent long-term facilitation following intermittent hypoxia is an important example of such plasticity, and a model that can account for this adaptive behavior is discussed. (iii) Where and how are the regulated variables CO2 and pH sensed? These sensors are essential if breathing is to be appropriate for metabolism. Neurons with appropriate chemosensitivity are spread throughout the brainstem; their individual properties and collective role are just beginning to be understood.

Breathing: Rhythmicity, plasticity, chemosensitivity

Intermittent hypoxia elicits long-term facilitation (LTF), a persistent augmentation (hours) of respiratory motor output. Considerable recent progress has been made toward an understanding of the mechanisms and manifestations of this potentially important model of respiratory plasticity. LTF is elicited by intermittent but not sustained hypoxia, indicating profound pattern sensitivity in its underlying mechanism. During intermittent hypoxia, episodic spinal serotonin receptor activation initiates cell signaling events, increasing spinal protein synthesis. One associated protein is brain-derived neurotrophic factor, a neurotrophin implicated in several forms of synaptic plasticity. Our working hypothesis is that increased brain-derived neurotrophic factor enhances glutamatergic synaptic currents in phrenic motoneurons, increasing their responsiveness to bulbospinal inspiratory inputs. LTF is heterogeneous among respiratory outputs, differs among experimental preparations, and is influenced by age, gender, and genetics. Furthermore, LTF is enhanced following chronic intermittent hypoxia, indicating a degree of metaplasticity. Although the physiological relevance of LTF remains unclear, it may reflect a general mechanism whereby intermittent serotonin receptor activation elicits respiratory plasticity, adapting system performance to the ever-changing requirements of life.

Invited Review: Intermittent hypoxia and respiratory plasticity

The respiratory response to hypoxia in mammals develops from an inhibition of breathing movements in utero into a sustained increase in ventilation in the adult. This ventilatory response to hypoxia (HVR) in mammals is the subject of this review. The period immediately after birth contains a critical time window in which environmental factors can cause long-term changes in the structural and functional properties of the respiratory system, resulting in an altered HVR phenotype. Both neonatal chronic and chronic intermittent hypoxia, but also chronic hyperoxia, can induce such plastic changes, the nature of which depends on the time pattern and duration of the exposure (acute or chronic, episodic or not, etc.). At adult age, exposure to chronic hypoxic paradigms induces adjustments in the HVR that seem reversible when the respiratory system is fully matured. These changes are orchestrated by transcription factors of which hypoxia-inducible factor 1 has been identified as the master regulator. We discuss the mechanisms underlying the HVR and its adaptations to chronic changes in ambient oxygen concentration, with emphasis on the carotid bodies that contain oxygen sensors and initiate the response, and on the contribution of central neurotransmitters and brain stem regions. We also briefly summarize the techniques used in small animals and in humans to measure the HVR and discuss the specific difficulties encountered in its measurement and analysis.

The Ventilatory Response to Hypoxia in Mammals: Mechanisms, Measurement, and Analysis

Intermittent hypoxia (IH) has been the subject of considerable research in recent years, and triggers a bewildering array of both detrimental and beneficial effects in multiple physiological system...

Therapeutic potential of intermittent hypoxia: a matter of dose.

Diamond possesses extraordinary material properties, a result that has given rise to a broad range of scientific and technological applications. This study reports the successful production of high-quality single-crystal diamond with microwave plasma chemical vapor deposition (MPCVD) techniques. The diamond single crystals have smooth, transparent surfaces and other characteristics identical to that of high-pressure, high-temperature synthetic diamond. In addition, the crystals can be produced at growth rates from 50 to 150 μm/h, which is up to 2 orders of magnitude higher than standard processes for making polycrystalline MPCVD diamond. This high-quality single-crystal MPCVD diamond may find numerous applications in electronic devices as high-strength windows and in a new generation of high-pressure instruments requiring large single-crystal anvils.

https://www.pnas.org/content/pnas/99/20/12523.full.pdf

Very high growth rate chemical vapor deposition of single-crystal diamond

Luminescence studies have been performed on phosphorous-doped diamond films deposited by hot-filament chemical vapor deposition. A broad luminescence band, centered around 1.9 eV is revealed, in the cathodo luminescence spectra of homoepitaxial and polycrystalline films, whereas the blue band-A luminescence, which is characteristic for undoped diamond, is quenched in the presence of phosphorus. The 1.9 eV luminescence band could not be excited by Ar+ laser light (2.54 eV) and did not show a zero-phonon line in the spectrum. Therefore, we suggest that this band is a red form of band-A luminescence, related to electron-hole recombination at substitutional phosphorous and a phosphorus-vacancy complex.

/pdf/red-luminescence-in-phosphorous-doped-chemically-vapor-5figrsr41j.pdf

S. M. Olsthoorn

Papers

Red luminescence in phosphorous-doped chemically vapor deposited diamond